PROJECT SUMMARY Early detection of response to spinal cord injury (SCI) therapeutic intervention programs is vital, as it will enable early termination of intervention in non-responding patients, prevent unnecessary financial burden, and allow for timely program modifications. In this project, we propose that resting state functional MRI (rsfMRI) can be used to detect early brain functional network changes that occur during an intervention, and that the changes will be predictive of recovery in chronic SCI patients. The long-term goal of this study is to establish rsfMRI as a new imaging biomarker that is predictive of progress towards recovery in response to therapy. International Standard of Neurological Classification for Spinal Cord Injury (ISNCSCI) scoring system is the most widely used clinical classification system of SCI that describes neurological injury level and degree of functional preservation. It is also used to monitor the progress and response to interventions such as functional electrical stimulation (FES) therapy. However, monitoring responses using ISNSCI is challenging because its ability to describe the degree of functional loss is limited. Therefore, there is a need in the field of SCI for a biomarker that is more sensitive to changes in function. In Aim 1 of this project, we will characterize the baseline time profile of the cortical reorganization in chronic SCI patients that occurs during a 4-weeks program of passive FES cycling, where movement is driven only by the cycle?s motor (no electric stimulation). RsfMRI data of the patients acquired at weeks 0, 2, and 4 will be analyzed to perform functional parcellation of the sensorimotor cortex, using the independent component analysis (ICA) and spectral clustering analysis (SCA) methods. BNC measures of the resulting sensorimotor cortex parcels will then be calculated. ISNCSCI scores of the patients will also be measured at weeks 0, 2, and 4, to test the hypothesis that we will observe minimal to no changes in sensorimotor cortex BNC and ISNCSCI scores of the patients after 4 weeks of passive FES cycling. In Aim 2 of this project, we will characterize the time profile of the cortical reorganization in chronic SCI patients that occurs during the four-week (active) FES cycling. Specifically, we predict that we will observe early functional network changes in the sensorimotor cortex of SCI patients (measured using BNC) at week 2 of the four-week FES cycling program, which will be predictive of changes in ISNSCI scores (neurological outcomes) at week 4. If successful, the study will: 1) provide a new and effective clinical tool to study plastic cortical changes that occur after SCI, 2) provide a new non-invasive imaging biomarker that is predictive of progress towards recovery in response to therapy, and 3) extend our knowledge about the functional reorganization that takes place during and after therapeutic intervention.